Leukemia Clinical Care 2

Question 1

Study that was crucial in making Imatinib the standard treatment for CML, instead of IFN + Ara-C?

Answer 1

IRIS Study: showed significant improvement in treatment outcome

(progression-free survival at 18 mo.)

Question 2

What are the 2 other tyrosine kinase inhibitors (2nd generation)?

Answer 2

1. Nilotinib
2. Dasatinib

Question 3

Answer 3

wet purpura (blood blister)

Question 4

Answer 4

Acute Myeloid leukemia

Question 5

Answer 5

Acute Myeloid Leukemia

Question 6

Answer 6

AML

(CD13 & CD33 positive distinguish myeloid cells from T cell or B cell)

Question 7

Acute Myeloid Leukemia median age of onset

Answer 7

67 yo

(M:F = 1:1)

Question 8

Predisposing factors to AML (5)

Answer 8

1. radiation
2. benzene
3. myeloproliferative or myelodysplastic syndromes
4. congenital DNA repair disorder
5. smoking (2 fold increase)

Question 9

How do you determine a good or poor prognosis in AML?

Answer 9

Cytogenetic analysis

Question 10

How does the WHO classify AML?

Answer 10

1. Recurrent genetic abnormalities
2. Multilineage dysplasia
3. Therapy-related
4. ambiguous lineage (lymphoid + myeloid lineage)

Question 11

Recurrent genetic abnormalities (AML) with a good prognosis (3)

Answer 11

1. t(15;17) → PML/RARa
2. inv 16 → CBFb/MYH11
3. t(8:21) → AML/ETO

(11q23 → MLL is less common)

Question 12

AML tx phases (2)

Answer 12

1. remission induction phast : lower leukemia burden from 10¹² → 10⁹
2. post-remission therapy: cure

Question 13

AML tx

Answer 13

combo chemo: cytarabine + anthracycline (aka “7 + 3”)

(Complete remission (CR) depending on age - 80% if < 60 yo; ~45% if > 60 yo)

Question 14

Acute Promyelocytic Leukemia (APL) -M3 translocation

(used to be called AML-M3)

Answer 14

t (15;17)

PML-RAR fusion

(blocks neutrophils from differentiation)

Question 15

Answer 15

Auer rods (aka “faggot cells”)

APL - M3

Question 16

Why do elderly patients have a poor AML prognosis (4)?

Answer 16

1. emerge from antecedent hematologic disorder
2. karyotype abnormalities
3. express MDR genes
4. co-morbidities

Question 17

Evaluation of AML in the elderly

Answer 17

1. ECOG PS
2. ADLs
3. Charleston comorbidity scores (to decide if chemo is approps)

Question 18

Elderly patients may receive chemo tx for AML if they meet which criteria (3)?

Answer 18

1. up to age 70 w/good PS
2. independent ADLS
3. low morbidity

Question 19

Geriatric patient AML Tx

Answer 19

hypomethylating agents (low dose chemo)

Question 20

Acute Lymphoblastic Leukemia prognosis: children vs. adults

Answer 20

• children ~ 80% cure
• adults ~ 30% cure

Question 21

Acute lymphoblastic leukemia sx (5)

Answer 21

1. cytopenia (bone marrow failure)
2. CNS involvement
3. bleeding
4. organomegaly
5. lymphadenopathy

(B symptoms: fever, sweats, weight loss)

Question 22

Poor prognostic factors for ALL

Answer 22

1. over 60 yo 10-15% survival
2. B cell: > 30 x 10⁹; T cell: >100 x 10⁹
3. Ph - ALL

AYA (adolescent & young adults - 15-39 y/o) do better

Question 23

Favorable cytogenetic abnormalities with ALL

Answer 23

hyperdiploid; del9p

Question 24

Cytogenetic abnormalities w/poor prognosis w/ALL

Answer 24

1. Ph +ALL t(9;22)
2. Ph - ALL:

• t(4;11) KMTZA translocation
• t(8;14) complex karyotype
• hypodiploid (30-39 chromosomes); near triploidy (60-78 chromosomes)

Question 25

1st line therapy for B cell ALLs are based on ____ (2).

Answer 25

1. phase (initiation, consolidation, maintenance, CNS prophylaxis) 2. population-based (peds, AYA, Ph+ ALL)

Question 26

T-cell ALL relapse tx

Answer 26

Nelarabine (purine nucleoside analogue) (prodrug; not curative)

Question 27

BiTE

Answer 27

Bispecific T-cell Engager: tethers T cell to cancer cell → engages & kills

Question 28

Leukostasis

Answer 28

symptomatic hyperleukocytosis (\>100,000/uL can be asymptomatic, if not → leukostasis) (seen in AML & CLL)

Question 29

CLL typically have a WBC count of

Answer 29

\>400,000/uL (low plts, low Igs)

Question 30

Why is leukostasis bad?

Answer 30

increases viscosity → local hypoxemia → release of cytokines → coagulation cascade or bleeding (HA, SOB)

Question 31

Answer 31

Pulmonary leukostasis (infiltration)

Question 32

Answer 32

neurologic infarct | (result of leukostasis)

Question 33

Why is this increased “buffy coat” bad?

Answer 33

it can cause an error in the reading of other blood components

Question 34

Spurious Lab Tests

Answer 34

marked leukocytosis: hyperkalemia, hypoxemia , hypoglycemia